The use of tannate salts of active pharmaceutical ingredients is well known. U.S. Pat. No. 6,287,597 describes tannate products containing pyrilamine tannate and phenylephrine tannate. The January 1990 issue of Annals of Allergy, Volume 64, describes combinations of chlorpheniramine tannate, pyrilamine tannate and phenylephrine tannate. An article in Clinical Medicine, dated September 1965, pages 1475-1478, describes tablets of pyrilamine tannate, chlorpheniramine tannate and amphetamine tannate. Phenylephrine tannate compositions are disclosed in U.S. Pat. No. 5,599,846 and phenylephrine tannate and chlorpheniramine tannate compositions are disclosed in U.S. Pat. No. 6,037,358. None of these references describe the problems with tannate pharmaceutical products caused by the large size of the tannate molecule. Because of its size, the percentage of active free base within the tannate salt is significantly lower than that in other salt forms such as the hydrochloride or maleate. The presence of low active percentages and the variable purity of the commercially available tannate salts leads to the stoichiometry of the active free base to tannic acid in the tannate salts to vary from batch to batch. This problem was noted in U.S. Pat. Nos. 5,599,846 and 5,663,415. This causes significant processing problems during manufacture and increases the likelihood that commercially available pharmaceutical products contain variable and in some instances, sub-therapeutic levels of the active drug substances creating dosing problems. None of these references suggest or describe pharmaceutical compositions containing tannate salts of active ingredients that are prepared with reduced variability in active drug content and increased certainty that the active drug is delivered within the therapeutic range. Also, none of the references suggest or describe tannate pharmaceutical compositions in the therapeutic classes of active ingredients for antinausea, antiemetic, antiinsomnia analgesics, or anticonvulsives.
None of the references discussed above suggest or describe the production of a tannate composition by means of an in-situ conversion of the active ingredient to the tannate salt in the presence of a dispersing agent using the method described herein to provide a dosage form which affords a sustained release of the active ingredient over prolonged intervals of time. Since the prolonged drug release character of the tannate salt enables the development of less frequent dosing regimens, such a composition is needed to improve patient compliance with dosage requirements.